CDK8 사용 가능한 구조물 PDB 직교 검색: PDBe RCSB PDB ID 코드 목록 3RGF , 4F6S , 4F6U , 4F6W , 4F70 , 4F7J , 4F7L , 4F7N , 4F7S , 4G6L , 4CRL , 5HBH , 5CEI , 5FGK , 5HBE , 5BNJ , 5HBJ , 5HVY , 5HNB , 5I5Z
식별자 별칭 CDK8 외부 ID OMIM : 603184 MGI : 1196224 HomoloGene : 55565 GeneCard : CDK8 직교체 종 인간 마우스 엔트레스 앙상블 유니프로트 RefSeq(mRNA) RefSeq(단백질) 위치(UCSC) Cr 13: 26.25 – 26.41Mb Cr 5: 146.17 – 146.24Mb PubMed 검색[3] [4] 위키다타
세포분열단백질키나아제8 은 인간에게 CDK8유전자 에 의해 암호화된 효소 다.[5] [6]
함수 이 유전자가 인코딩한 단백질은 사이클린 의존성 단백질키나아제(CDK) 계열의 일원이다. CDK8과 Cyclin C 는 중재자 콤플렉스와 연관되어 있으며, 몇 가지 메커니즘에 의해 전사 를 규제한다. CDK8은 여러 개의 전사 인자에 바인딩되며, 이는 전사 인자 함수에 활성화 또는 억제 효과를 가질 수 있다.[7] [8] CDK8 인산염은 노치 세포 내 도메인,[9] SREBP ,[10] STAT1 S727을 나타낸다.[11] 또한 CDK8은 중재자 복합 테일 모듈의 서브유닛 교체 에 영향을 주어 전사 활성화를 억제한다.[12] [13] 또한 CDK8은 RNA 중합효소 II 의 중재자 콤플렉스에 대한 결합에 영향을 미친다.[14] [15]
임상적 유의성 CDK8은 대장암 종양 유전자로 인간 대장종양에서 CDK8 유전자가 증폭되어 대장 종양에 작용하는 β-카테닌 매개 전사가 활성화된다.[16] 단, CDK8은 모든 세포 유형에서 인큐베이터가 아닐 수 있으며, 실제로 노치 및 EGFR 신호 경로에서 종양 억제기 역할을 할 수 있다. 구체적으로 CDK8은 노치 세포내 영역의 이전 을 촉진하고,[9] C. 에글레건 EGFR 신호 중심 세포 운명도 억제한다.[13] 따라서 CDK8 은 Wnt /β-카테닌 신호에 의해 구동되는 암의 종양 억제 유전자가 될 수 있지만, 대신 노치 또는 EGFR 신호 에 의해 구동되는 암의 종양 억제 유전자 가 될 수 있다. 게다가, CDK8,[17] 대한 연구가 다른 조직에서 CDK8 억제의 영향을 묘사하기가 필요하다 그것이 그렇게 시간 동안, 약 암 치료에 대하CDK8을 목표로 하고 h.에서 검증되지 않은 남아 있는 종양 억제에 중요한 역할을 하고 있는지 여부를 나타내는 값 전사 활성화는 종양 억제 유전자 p53단백질에 의해 추진합니다.uma ns.
키나제 영역의 ATP 바인딩 포켓의 돌연변이와 관련된 자가 우성 증후군이 설명되었다.[18] 임상적 특징으로는 말뭉치 의 아게네시스, 경증에서 온건한 지적 장애, 저혈압 , 발작 , 청각 또는 시각 장애, 행동 장애, 변성 안면 이상증, 선천성 심장 질환, 무정형 기형이 있다.
잠재적인 약물 목표로서 천연물 코티스타틴 A 는 CDK8과 CDK19 의 강력한 선택적 억제제다.[19] CDK8과 CDK19를 코티스타틴A로 억제하면 AML 세포 성장을 억제하고 세포 정체성 유전자 CEBPA 와 IRF8 을 포함한 초한증 관련 유전자의 선택적 불균형적인 조절을 유발하여 AML의 동물 모델에서 항암 활성을 가진다.
상호작용 Cyclin 의존성 키나제 8은 다음과 상호작용 하는 것으로 나타났다.
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